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Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus

Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca(2+) channel blocker nimodipine. We hypothesized that treatment with nimodipine would be also beneficial to young ferrets with kaolin-induced hydrocephalus. Hydroc...

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Autores principales: Di Curzio, Domenico L., Mao, Xiaoyan, Baker, Aidan, Del Bigio, Marc R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932868/
https://www.ncbi.nlm.nih.gov/pubmed/29720231
http://dx.doi.org/10.1186/s12987-018-0099-0
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author Di Curzio, Domenico L.
Mao, Xiaoyan
Baker, Aidan
Del Bigio, Marc R.
author_facet Di Curzio, Domenico L.
Mao, Xiaoyan
Baker, Aidan
Del Bigio, Marc R.
author_sort Di Curzio, Domenico L.
collection PubMed
description Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca(2+) channel blocker nimodipine. We hypothesized that treatment with nimodipine would be also beneficial to young ferrets with kaolin-induced hydrocephalus. Hydrocephalus was induced at 14 days of age and animals were treated either with vehicle, low dose nimodipine (3.2 mg/kg/day), or high dose nimodipine (16 mg/kg/day) for 2 weeks from 38 to 52 days age. Hydrocephalic ferrets developed progressive ventriculomegaly, behavioral changes, and in some cases cortical blindness. These changes were not ameliorated by nimodipine. Histological examination showed damage in periventricular white matter, corpus callosum thinning, axonal damage, reactive astroglial changes, and suppressed cell proliferation compared to non-hydrocephalic controls. Treatment with nimodipine was not beneficial for any of the pathological changes mentioned above; only low dose nimodipine treatment was associated with normalized content of glial fibrillary acidic protein, despite larger ventricles. We conclude that young hydrocephalic ferrets experience behavioral impairments and structural brain damage that are not consistently improved by intermittent nimodipine treatment. Continuous delivery should be considered in further preclinical studies.
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spelling pubmed-59328682018-05-09 Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus Di Curzio, Domenico L. Mao, Xiaoyan Baker, Aidan Del Bigio, Marc R. Fluids Barriers CNS Short Paper Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca(2+) channel blocker nimodipine. We hypothesized that treatment with nimodipine would be also beneficial to young ferrets with kaolin-induced hydrocephalus. Hydrocephalus was induced at 14 days of age and animals were treated either with vehicle, low dose nimodipine (3.2 mg/kg/day), or high dose nimodipine (16 mg/kg/day) for 2 weeks from 38 to 52 days age. Hydrocephalic ferrets developed progressive ventriculomegaly, behavioral changes, and in some cases cortical blindness. These changes were not ameliorated by nimodipine. Histological examination showed damage in periventricular white matter, corpus callosum thinning, axonal damage, reactive astroglial changes, and suppressed cell proliferation compared to non-hydrocephalic controls. Treatment with nimodipine was not beneficial for any of the pathological changes mentioned above; only low dose nimodipine treatment was associated with normalized content of glial fibrillary acidic protein, despite larger ventricles. We conclude that young hydrocephalic ferrets experience behavioral impairments and structural brain damage that are not consistently improved by intermittent nimodipine treatment. Continuous delivery should be considered in further preclinical studies. BioMed Central 2018-05-03 /pmc/articles/PMC5932868/ /pubmed/29720231 http://dx.doi.org/10.1186/s12987-018-0099-0 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Paper
Di Curzio, Domenico L.
Mao, Xiaoyan
Baker, Aidan
Del Bigio, Marc R.
Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus
title Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus
title_full Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus
title_fullStr Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus
title_full_unstemmed Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus
title_short Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus
title_sort nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus
topic Short Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932868/
https://www.ncbi.nlm.nih.gov/pubmed/29720231
http://dx.doi.org/10.1186/s12987-018-0099-0
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